Hepatocellular carcinoma (HCC), commonly referred to as liver cancer, is the sixth most common cancer worldwide in terms of numbers of cases (626,000 or 5.7% of new cancer cases in 2002). Parkin D M et al., CA Cancer J Clin 2005; 55:74-108. In the United States, the reported incidence has increased to 4.7/100,000 persons. HCC is a malignant tumor associated with high mortality and, because of the very poor prognosis, the number of deaths (598,000 in 2002) is almost the same each year as the number of new cases reported (Parkin D M et al., CA Cancer J Clin 2005; 55:74-108). The high mortality rate makes HCC the third most common cause of death from cancer. This unfortunate high rate of death is largely attributed to late diagnosis of this tumor as patients are usually in an advanced stage when first diagnosed.
HCC is often refractory to all current chemotherapies. Four major categories of treatment modalities are commonly offered to HCC patients: (1) surgical operations including tumor resection and liver transplantation; (2) percutaneous approaches, such as radiofrequency ablation; (3) transarterial interventions, such as embolization and chemoembolization; (4) molecular and medicinal therapies with the use of tagged antibody and drug medication. Unfortunately, there is no definite cure for HCC patients. Surgical resection is presently an effective means for removing tumor nodules; however, it is not applicable to late-staged HCC patients with large and multiple lesions and patients with distant metastases. Other treatment approaches, such as transarterial interventions, suffer from low response rate. Systemic chemotherapy has not been shown to be effective for the treatment of nonresectable HCC. Due to high recurrence rate after curative treatment, 5-year survival rate remains sub-optimal, at about 15%, for HCC patients after initial diagnosis. Ultimately, liver transplantation remains the best therapeutic intervention that offers the longest disease-free survival. Thus there remains a need for additional means for diagnosing, prognosing, and treating HCC.
Current surveillance program for diagnosing liver cancers relies mainly on detection of serum alpha-fetoprotein (AFP) and ultrasound imaging. However, serological level of AFP is inaccurate in detecting liver tumors, suffering from low sensitivity, when the cut-off level of AFP is at 20 ng/ml (Debruyne E N and Delanghe J R, Clin Chim Acta, 395: 19-26 (2008)), and non-specific in differentiating liver tumors from other malignancies as well (Marrero J A, Curr Opin Gastroenterol 19(3):243-249, 2003). Other imaging technologies, such as magnetic resonance imaging, angiography, computed tomography, are frequently employed to spot liver nodules, but these are usually only performed after other symptoms or positive screening have occurred. Current analyses often vary and are highly operator dependent.
Therefore, the objectives of the present invention are to provide an improved method of diagnosing liver cancer at an early stage and to identify new targets for liver cancer therapy.